Learning and memory are impaired in aged rodents and humans. To elucidate the mechanisms underlying these impairments, research has focused on the hippocampal formation, a region that is critical for certain forms of learning and memory. While data indicate that the physiological parameters of hippocampal neurons change with age, very little is known about the structure and function of individual neurons in the aged. Therefore, the main objective of this application is to determine how dendritic structure and function change in the hippocampal formation of aged mice. Experiments proposed here are designed to test the hypotheses that dendritic trees increase in size, while excitatory synaptic contacts decrease, and that such changes impair the function of single neurons in the aged hippocampal formation. The first specific aim is to test the hypothesis that dendritic length increases in the hippocampus of aged male mice. Neurons from young adult, older adult and aged male mice will be labeled using several methods, including the use of novel transgenic mice that express green fluorescent protein in some neurons. Dendritic trees will be quantified in three dimensions. The second specific aim is to test the hypothesis that the density of excitatory synapses on hippocampal neurons decreases in the aged male mouse, while the density of inhibitory synapses does not change. The densities of spines and synapses will be quantified on the same neurons analyzed under specific aim 1. The third specific aim is to test the hypothesis that morphological changes in aged mice lead to less effective integration of synaptic currents, and hence impaired neuronal function. Physiological and morphological data from neurons in adult and aged mice will be combined to construct computational models that will be used test this hypothesis. Results of this study will determine whether structural changes in individual dendritic trees could lead to functional impairments in hippocampal neurons in aged mice. We regard this as a first step in elucidating whether functional changes in single neurons may underlie the behavioral deficits seen during human aging.